In bone, the bisphosphonates act as phosphate surrogates. They are complexed with calcium in the hydroxyapatie matrix and, once incorporated into the mineral phase of bone, act to inhibit osteoclastic bone resorption. Because there are "dedicated" matrix-resorbing cells in plaque as there are in bone, we postulate that bisphosphonates associated with the hydroxyapatite matrix of mature atherosclerotic plaque will have a similar effect on the accumulation of calcified matrix in the plaque as they do in bone.